By showing scientists precisely how tumor cells travel, the tool may help them plot new strategies for preventing metastasis, which leads to more than 90 percent of cancer deaths.

“There’s still so much we don’t know about exactly how tumor cells migrate through the body, partly because, even using our best imaging technology, we haven’t been able to see precisely how these individual cells move into blood vessels,” says lead researcher Andrew D. Wong, a graduate student in materials science and engineering at Johns Hopkins University.

“Our new tool gives us a clearer, close-up look at this process.”

SEE THE STEPS
Researchers can now record video of individual human breast cancer cells crawling through a three-dimensional collagen matrix. The material resembles the human tissue that surrounds tumors when cancer cells break away and try to relocate elsewhere. The process is called invasion.

Wong also collected video of single cancer cells prying and pushing their way through the wall of an artificial vessel lined with human endothelial cells, the kind that line human blood vessels. Entering the bloodstream through this process, called invasion, cancer cells can hitch a ride to other parts of the body and begin to form deadly new tumors.

Wong then replicated the processes in a small transparent chip that incorporates the artificial blood vessel and the surrounding simulated tissue material. A nutrient-rich solution flows through the artificial vessel, mimicking the properties of blood.

The breast cancer cells, inserted individually and in clusters in the tissue near the vessel, are labeled with fluorescent tags, enabling them to be seen, tracked, and recorded by a microscopic viewing system.

Wong took on the project nearly five years ago and ultimately produced impressive results, says Peter Searson, a professor in the Whiting School of Engineering and Wong’s doctoral advisor.

“Andrew was able to build a functional artificial blood vessel and a micro environment that lets us capture the details of the metastatic process. In the past, it’s been virtually impossible to see the steps involved in this process with this level of clarity. We’ve taken a significant leap forward.”

ENTER THE BLOODSTREAM
Cancer researchers should now have a much clearer look at the complex physical and biochemical interplay involved in leaving a tumor, moving through surrounding tissue, and approaching a blood vessel.

The inventors have already captured detailed images of a cancer cell finding a weak spot in a vessel wall, exerting pressure, and squeezing through far enough so that the passing current of simulated blood swept it away.

“Cancer cells would have a tough time leaving the original tumor site if it weren’t for their ability to enter our bloodstream and gain access to distant sites,” Wong says. “So it’s actually the entry of cancer cells into the bloodstream that allows the cancer to spread very quickly.

“This device allows us to look at the major steps of metastasis as well as to test different treatment strategies at a relatively fast pace.

“If we can find a way to stop one of these steps in the metastatic cascade, we may be able to find a new strategy to slow down or even stop the spread of cancer.”

Next, the researchers plan to use the device to try out various cancer-fighting drugs within this device to get a better look at how the medications perform and how they might be improved.

The device is protected by a provisional patent. A grant from Johns Hopkins’ Institute for NanoBioTechnology and a National Cancer Institute grant supported the work.

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